期刊
BIOORGANIC CHEMISTRY
卷 94, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2019.103389
关键词
alpha-Synuclein aggregation; Parkinson's disease; O-GlcNAcylation; Neurodegenerative diseases
资金
- Australian Research Council Discovery Early Career Research Award [ARC DECRA: DE140101632]
- Griffith University Postgraduate Research Scholarship (GUPRS)
- Menzies Health Institute Queensland (MHIQ), Griffith University Collaborative Interdisciplinary Grants
Numerous post-translational modifications (PTMs) of the Parkinson's disease (PD) associated alpha-synuclein (alpha-syn) protein have been recognised to play critical roles in disease aetiology. Indeed, dysregulated phosphorylation and proteolysis are thought to modulate a-syn aggregation and disease progression. Among the PTMs, enzymatic glycosylation with N-acetylglucosamine (GlcNAc) onto the protein's hydroxylated amino acid residues is reported to deliver protective effects against its pathogenic processing. This modification has been reported to alter its pathogenic self-assembly. As such, manipulation of the protein's O-GlcNAcylation status has been proposed to offer a PD therapeutic route. However, targeting upstream cellular processes can lead to mechanism-based toxicity as the enzymes governing O-GlcNAc cycling modify thousands of acceptor substrates. Small glycopeptides that couple the protective effects of O-GlcNAc with the selectivity of recognition sequences may prove useful tools to modulate protein aggregation. Here we discuss efforts to probe the effects of various O-GlcNAc modified peptides on wild-type alpha-synuclein aggregation.
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